Table 2.

Clinical studies of MSC therapy for hemorrhagic stroke

Patient population	Stem cell type	Stroke subtype	Dose, administration, and timing	Follow-up	Functional results and side effects	Ref
12 patients (including 6 controls) 4 females (all MSC group) 8 males, 20–60 years old	Autologous bone marrow-derived MSCs	2 (hemorrhage), 4 (ischemia)	50–60 × 106 cells, via IV administration, 3 months-1 year post-stroke	8 and 24 weeks	No improvement in all clinical scores (FM and BI) and functional imaging parameters at 8 and 24 weeks; no adverse events	73
10 patients, no controls, 6 females, 4 males, 42–87 years old	Combined olfactory ensheathing cells (OEC), neural progenitor cells (NPC), umbilical cord mesenchymal cells (UCMSCs), and Schwann cells (SC)	6 (cerebral infarct), 4 (hemorrhage)	OEC: 1 × 106, OEC + NPC: 1–2 × 106 and 2–4 × 106, NPC: 2–5 × 106, NPC + SC: 2–5 × 106 and 2 × 106, UCMSCs:1–2.3 × 107, via intracranial parenchymal implantation (perilesion) (OEC, NPC), intrathecal implantation (NPC, SC), and intravenous administration (UCMSCs), 6 months-20 years post-stroke	6 months - 2 years	Improvement in neurological function including improved speech, muscle strength, muscular tension, balance, pain, and breathing; increased BI scores and Clinic Neurologic Impairment Scale score; no adverse events	75
100 patients (including 40 controls), 40 females, 60 males, 35–74 years old	Autologous bone marrow mononuclear cells including MSCs	ICH (with surgical drainage and decompressive craniotomy)	7.25 × 105 to 1.35 × 106/L MSCs (3.5mls injected), via intracranial drainage tube (base ganglia), 5–7 days after ICH	6 months	Improvement in NIHSS and BI scores; 5 treatment group patients had low grade fever (3 days) which resolved without intervention; 1 patient was diagnosed with lung cancer 4 months after treatment	76
24 patients (including 8 controls), 8 females, 16 males, 38–58 years old	7 patients with autologous BM mononuclear cells, 9 patients with allograft umbilical cord mononuclear cells	Hemorrhage	1.8 × 108 of BM cells, via intracranial administration into hematoma cavity, 2 weeks then 3 weeks post hemorrhage	3, 6, 12, 36, and 60 months	Computed tomography (CT) scans for brain tissue healing showed better outcomes; improvements in NIHSS, mRS, and modified BI; no adverse events	74
9 patients (including 4 controls), 4 females, 5 males, 41–59 years old	Autologous BM-derived MSCs	ICH	4.57 × 107 MSCs per IV infusion was administered accounting to 8.54 × 105 per kilogram body weight in two occasions (4 weeks apart), > 1 year post ICH	12, 16, 24, 36 and 60 weeks	Improvements in motor disability and cognitive impairment; evident clinical improvement in patients of both groups were comparable; no adverse events	77
9 patients, 3 females, 6 males, 24–30 weeks old	Human umbilical cord-derived MSCs hours	IVH	3 patients received 5 × 106, 6 received 1 × 107, via intraventricular administration within 7 days of diagnosis	2, 4, 6 and 8 weeks	Safe and feasible; no adverse events	72

BI Barthel Index, BM bone marrow, FM Fugl-Meyer, CT computed tomography, ICH intracerebral hemorrhage, IV intravenous, IVH intraventricular hemorrhage, mRS modified Rankin Scale, NIHSS National Institute of Health Stroke Scale, NPC neural progenitor cells, OEC olfactory ensheathing cells, SC Schwann cells, UCMSCs umbilical cord mesenchymal stem cells